Phagolysosomal alterations induced by unleaded gasoline in epithelial cells of the proximal convoluted tubules of male rats: Effect of dose and treatment duration

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Abstract
Short‐term oral administration of unleaded gasoline to male rats reproduces the accumulation of phagolysosomes (hyaline droplets) in epithelial cells of the renal proximal convoluted tubules (PCT) observed following long‐term inhalation of wholly volatilized gasoline. Phagolysosomes are partially composed of α2u‐globulin, a low‐molecular‐weight protein, unique to male rats. In this study, dose‐dependent and chronologic alterations of phagolysosomes caused by gasoline were observed by transmission electron microscopy. Exposure to commercially available unleaded gasoline (0.4–2.0 ml/kg, po, once daily, 9 d) increased the number and size of phagolysosomes in epithelial cells of the PCX in male rat kidney. However, administration of 0.04 ml gasoline/kg or less was ineffective in inducing phagolysosomal accumulation. Sub‐cellular analysis revealed that many of the phagolysosomes observed in treated rats (doses greater than 0.4 ml/kg) were angular and had cross‐sectional diameters varying from 0.5 to 9 μm; in controls the majority of phagolysosomes were round and their diameter varied from 0.5 to 2.5 μm. Treatment of male rats with gasoline (2.0 ml/kg body weight, po, 1–9 d) caused a progressive increase in the number and size of phagolysosomes in PCX epithelial cells dependent on treatment duration. Alterations in phagolysosomal morphology and quantity occurred within 20 h following a single dose of gasoline, emphasizing that the process of phagolysosome accumulation is a dynamic phenomenon. Many of the enlarged phagolysosomes contained a condensed, crystalline core of greater electron density than the surrounding matrix. Furthermore, the rapid increase in abnormal, condensed contents in the phagolysosomes may indicate that a derangement of renal protein catabolism is the primary mechanism by which fuel hydrocarbons cause hyaline droplet nephropathy in male rats.